Nitric oxide decreases myofibrillar CA++ sensitivity in skeletal muscle

F. H. Andrade, H. Westerblad, M. B. Reid

Research output: Contribution to journalArticlepeer-review


Nitric oxide (NO) seems to modulate skeletal muscle function by inhibiting force production (Nature 373:546, 1994). In this study, we tested the hypothesis that NO would decrease force in isolated single skeletal muscle fibers by diminishing cytosolic Ca++ concentration, [Ca++]. Methods: Single skeletal muscle libers (n=17) were isolated from flexor brevis of male mice and microinjected with indo-1, a fluorescent Ca++ indicator The responses of [Ca++]i and force to SNAC (250-1000 μM) were measured during brief (350 ms) submaximal contractions. Force/Ca++ relationships were obtained by inducing contractions at different stimulation frequencies and the results fitted to a Hill equation. Maximal Ca++-activated force was determined during incubation with 10 mM caffeine and 100 Hz stimulation, before and during exposure to SNAC. Results: Submaximal force showed large variability during exposure to SNAC, with a mean increase of 6% (P= not significant). [Ca++]i, on the other hand, increased from 466±21 nM to 524±37 nM (P<0.05). SNAC also changed the force/[Ca++]i relationship: the [Ca++]i giving 50% of maximal force (Ca50) increased from 436±18 nM to 494±28 nM (P<0.05). Maximal force during SNAC exposure was 98.4±0.5% of baseline (P=not significant). Conclusions: We reject our original hypothesis because the NO donor SNAC increased [Ca++]i without affecting force. SNAC shifted the force/[Ca++]i relationship to the right, but it didn't alter the maximal Ca++-activated force (during caffeine exposure). These results suggest that NO has two opposing effects on contractile function: it increases Ca++ release and decreases myofibrillar Ca++ sensitivity.

Original languageEnglish
Pages (from-to)A54
JournalFASEB Journal
Issue number3
StatePublished - 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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